Saturday, August 29, 2015

I recently picked up this book (published a few years ago) by Elizabeth Tierney, which details the drawn-out loss of her husband to dementia.It is a book that sticks in the mind not just for its unflinching depiction of a pitiless disease (which I won't dwell on here), but also for the variability in the behaviour of those people charged with helping these patients.

The book opens with a description of the author's husband during his younger days. The author paints a picture of a cultured Irish
emigrant with a dull job and a wicked sense of humour, dividing his time
between the North and South of the USA, a life not unlike many others. The onset of symptoms of dementia sets off a string of visits to a variety of physicians. After many consultations and failures to respond to
medication, he is given a diagnosis of probable Lewy
body dementia. Even when this diagnosis is finally made, the author
expresses a nostalgia for ailments that receive a simple recommendation for
treatment. Like many people who suffer from Lewy body dementia, he has a bad
reaction to many of the medications used in trying to treat dementia and
associated problems that go with it, although the book doesn’t stray into an
anti-pharmacological polemic.

The bedside manner of at least some doctors, however, is another matter. Having sat in on a memory clinic that treats caregivers and
patients with respect, I found the behaviour of some physicians striking. Some
of the doctors the author encounters seem to automatically assume she should just allow her
husband to die. Another offers the author a recitation from The Bible. When she protests that she is not religious, the doctor replies that he is, and continues
unphased with his quotations.

The general financial challenge of a spouse with dementia is confronted (albeit in a family that are not as bad off as others), as well as the difficulty of finding good professional to act as home
help. Again, the lack of compassion of at least some of
the people who work in the area is striking (Oh, you mean speak to him like a REAL person?). When one reads
through the litany of reasons why various staff are rejected one can imagine how, from the outside, the author might come across as highly demanding as an individual.
Nonetheless, from inside the author's view, the demands of dementia quickly put this all back in context.

Towards the end, the author has received help from excellent doctors and assembled a good care team, and sometimes has a little more free time on her hands than she had earlier in the disease. One can understand how healthcare professionals can get jaded about "heartsink" conditions such as dementia, where the patient is unlikely to ever return to "normality". However, even in the absence of a cure for this disease, one comes away from this book thinking that there is much room for improvement in the consistency of how people with dementia and those that care for them are treated.

Sunday, August 16, 2015

Along with talking therapies, pharmacological approaches are often used to tackle depression. Selective serotonin reuptake inhibitors (SSRI's) are often a first choice for depression treatment, and while they work well for many people with depression, oftentimes they don't. When they are effective, SSRI's typically take weeks to kick in (an interesting recent paperhas suggested a possible reason why).

But other drugs are being used to fight depression. Although ketamine is known as a drug of abuse, it is also used for a number of medical purposes, including as an anaesthetic. However, at sub-anaesthetic doses, ketamine may also have antidepressant effects. For psychiatrists and their patients, the exciting aspect of ketamine is that it has a positive effect in many patients who do not respond to other antidepressants, and this alleviation of depression has been evident within a matter of hours rather than weeks. The downside is that this positive effect may not persist for much longer than a week, so repeated doses may be required to maintain the effect.

What may be driving the effect of ketamine? It has been suggested that brain-derived neurotrophic factor (or BDNF for short) may play a role in depression. BDNF is used in the maintenance and function of neurons, but chronic stress may reduce BDNF levels, and this could act as a mechanism through which long-term stress leads to depression. Previous evidencehas indicated that ketamine treatment can increase BDNF in people whose depression is alleviated by the drug. However, this previous study just looked a single dose.

A recent study from our group looked at multiple doses of ketamine, to examine whether multiple doses would lead to comparable effects on depression, and also on BDNF. Patients were recruited who had failed to respond to first-line pharmacological therapy-even after the time it would take to show an effect these classic antidepressants, they were still depressed. Ketamine was administered under controlled conditions, with doctors supervising patients for a sufficient length of time to ensure patients would be protected from any potential adverse effects. Patients reported on their levels of depression before and after three doses of ketamine, and blood samples were taken at these times to assess patient's levels of BDNF.

We defined a clinical response in depression severity as a 50% or more reduction in scores on the Hamilton Depression Rating Scale, a widely used scale for quantifying depression severity. Ketamine significantly improved depressive symptoms in a majority of patients, both after two hours and one week later, and this was the case after each dose. (It should be noted however that not all patients continued with a second or third dose).

As had previously been shown, BDNF was reduced in those suffering from depression at baseline compared to healthy controls. Ketamine increased BDNF at one week after the first dose in those patients whose depression was alleviated by ketamine. However, this rise in BDNF did not occur after a second or third dose. So, although ketamine was keeping depression levels down for most of these patients, BDNF was notshowing a persistent increase that mirrored this. The results, in this case, did not seem to support the idea that changes in BDNF goes hand-in-hand with an alleviation of depression.

As a comparison, we also looked at depression levels and BDNF in response to electroconvulsive therapy* (ECT), which is also used to treat depression in people who have not seen improvement after first-line treatment. Again, ECT was administered under controlled conditions, with patients being monitored for any side effects. Similar to ketamine, ECT reduced depression in the patient group. ECT did not increase BDNF at a one-week follow-up, although previous evidence has suggested that BDNF may be increased one month post-ECT.

Future research may tell us more about how ketamine has the rapid impact that it does upon depression. Understanding these mechanisms in greater depth may ultimately allow for treatments which target these mechanisms more specifically, thus minimising the risk of side effects.

*I should note here that although ECT has had a very negative portrayal in some classic films, ECT as it is administered today is not only effective, but is also not the painful experience one might see in a film, as patients are preparedby being given an anaesthetic and muscle relaxant before the procedure. Nonetheless, like other treatments for depression, it is still associated with the risk of side effects.